Hemiparesis of the upper limb is one of the most serious impairments resulting from stroke. Approximately 75% of the over 795,000 strokes that occur annually in the United States cause some degree of upper extremity paralysis. Up to 65% of stroke survivors still cannot use their affected hand to assist with activities of daily living 6 months after their stroke. The proposed project is a clinical trial that compares the effects of an innovative neuromuscular electrical stimulation therapy to a therapy that integrates the electrical stimulation with interactive hand therapy video games. The purpose of the proposed research is to address the need for effective upper limb rehabilitation therapies by evaluating the effects of these treatments on both hand and brain function. Contralaterally controlled functional electrical stimulation (CCFES) is an innovative neuromuscular electrical stimulation (NMES) treatment for improving recovery of hand function after stroke. CCFES stimulates the paretic hand to open in proportion to the degree of volitional opening of the contralateral unimpaired hand. This enables stroke patients to perform active repetitive hand opening exercises at home and practice functional tasks with a therapist in the lab. Significant improvements in dexterity, upper extremity impairment, and activity limitation measures have been shown with CCFES, but the magnitude of improvement depends on the severity and chronicity of impairment. It may be possible to improve outcomes in both moderately and severely impaired patients by increasing the motor relearning qualities of the home-based part of the treatment, which comprises 70% of the total treatment hours. Therefore, in this study, we integrate CCFES with custom-designed attention-engaging, goal-oriented, skill-requiring CCFES-assisted hand therapy video games (HTVG) and compare the effects of the combined treatment (CCFES+HTVG) to the effects of CCFES alone. The video game component is expected to enhance the treatment effect because the CCFES-mediated games are more goal-oriented and require greater motor planning, motor control, and concentration than CCFES-mediated repetitive hand opening exercises, and therefore may produce more adaptive neuroplastic effects in the brain. This project will enroll 52 chronic stroke patients and randomize them to 12 weeks of either CCFES+HTVG or CCFES in order to: 1) determine if integrating HTVG and CCFES leads to greater improvement in dexterity, impairment, activity limitation, and quality of life, 2) determine how severity of impairment and time post-stroke influences the relative effects of the treatments, thereby defining subpopulations most likely to benefit, and 3) elucidate and compare how the treatments affect cortical activation during a hand motor control task (fMRI assessment). This will be the first randomized controlled trial that integrates video games and neuromuscular electrical stimulation in such a way that the stimulation is delivered during play of the video games. This project is important to the field of neurorehabilitation because it recognizes the potential of combining synergistic therapies to achieve greater benefits for patients, and also recognizes the need to tailor therapies to patient characteristics in order to achieve the best possible outcomes.